Diphtheria, Tetanus, and Pertussis

Description

Diphtheria is an acute bacterial disease caused by toxigenic strains of Corynebacterium diphtheriae and occasionally C. ulcerans. It is transmitted through respiratory droplets and personal contact. Diphtheria affects the mucous membranes of the respiratory tract (respiratory diphtheria), the skin (cutaneous diphtheria), and occasionally other sites (eyes, nose, or vagina).

Tetanus, an acute disease caused by Clostridium tetani, is characterised by muscle rigidity and painful spasms, often starting in the muscles of the jaw and neck. Severe tetanus can lead to respiratory failure and death. The disease is caused by a neurotoxin produced by anaerobic tetanus bacilli growing in contaminated wounds. Lesions that are considered "tetanus prone" are wounds contaminated with dirt, feces or saliva, deep wounds, burns, crush injuries or those with necrotic tissue. However, tetanus has also been associated with apparently clean superficial wounds, surgical procedures, insect bites, dental infections, chronic sores and infections, and intravenous drug use. In 5%-10% of reported cases in the United States, no antecedent wound was identified.

Pertussis, caused by the bacterium Bordetella pertussis, is a highly communicable respiratory illness characterised by prolonged paroxysmal coughing. Persons in all age groups can be infected. Complications and deaths from pertussis are most common among unvaccinated infants.

Occurrence

Diphtheria remains a serious disease throughout much of the world. In particular, large outbreaks of diphtheria occurred in the 1990s throughout Russia and the other former Soviet republics. Most life-threatening cases occurred in inadequately immunised persons. Travellers to disease-endemic areas are at increased risk for exposure to toxigenic strains of C. diphtheriae. Areas with known endemic diphtheria include Africa — Algeria, Egypt, and the countries in sub-Saharan region; Americas — Brazil, Colombia, Dominican Republic, Ecuador, Haiti and Paraguay; Asia/South Pacific — Afghanistan, Bangladesh, Bhutan, Cambodia, China, India, Indonesia, Laos, Mongolia, Burma (Myanmar), Nepal, Pakistan, Papua New Guinea, Philippines, Thailand, and Vietnam; Middle East — Iran, Iraq, Syria, Turkey, and Yemen; Europe — Albania and all countries of the former Soviet Union.

Tetanus is a global health problem because C. tetani spores are ubiquitous. The disease occurs almost exclusively in persons who are inadequately immunised. In developing countries, tetanus occurring in neonates born to unvaccinated mothers (neonatal tetanus) is the most common form of the disease.

B. pertussis circulation occurs worldwide, but disease rates are highest among young children in countries where vaccination coverage is low. In developed countries, severe disease is usually limited to unvaccinated infants. Immunity from childhood vaccination, as well as from natural disease, wanes with time so adolescents and adults can become infected or re-infected.

Risk for Travellers

Diphtheria and pertussis are more frequent in parts of the world where vaccination levels are low. Tetanus can occur anywhere in the world in inadequately vaccinated persons.

Clinical Presentation

Diphtheria

The incubation period is 2-5 days (range 1-10 days); symptom onset is typically gradual. Early symptoms of respiratory diphtheria include malaise, sore throat, loss of appetite, and a moderate fever (rarely >103°F). If the larynx is involved, persons may become hoarse and have a barking cough. Within 2-3 days, an adherent, gray membrane forms over the mucous membrane of the tonsils and/or pharynx. Attempts to remove the membrane cause bleeding. Extensive membrane formation may result in airway obstruction. In severe cases of respiratory diphtheria, there is cervical lymphadenopathy and a swollen neck ("bull-neck" appearance). Toxin absorbed from the respiratory tract can cause serious complications, including myocarditis and neuropathies. The case-fatality rate of respiratory diphtheria is 5%-10%. Cutaneous diphtheria is characterised by a scaling rash or chronic nonhealing ulcers with a gray membrane. Cutaneous and nasal diphtheria are localized infections rarely associated with systemic toxicity.

Tetanus

There are three clinical syndromes associated with tetanus infection: 1) generalised, 2) localized, and 3) cephalic. Generalised tetanus is the most common form, accounting for more than 80% of cases. In generalised tetanus, the average incubation period between injury and symptom onset is 7-8 days (range 3 days-3 weeks). The most common initial sign is trismus (spasm of the muscles of mastication or "lockjaw"). Trismus may be followed by painful spasms in other muscle groups in the neck, trunk, and extremities and by generalised tonic tetanic seizure-like activity or frank convulsions in severe cases. Generalised tetanus can be accompanied by autonomic nervous system abnormalities, as well as a variety of complications related to severe spasm and prolonged hospitalization. Neonatal tetanus is generalised tetanus occurring in neonates, usually due to umbilical stump infections. The clinical course of generalised tetanus is variable and depends on the degree of prior immunity, the amount of toxin present, and the age and general health of the patient. Even with modern intensive care, generalised tetanus is associated with mortality rates of 10%-20%.

Localized tetanus is an unusual form of the disease consisting of spasm of muscles in a confined area close to the site of the injury. Although localized tetanus often occurs in persons with partial immunity and is usually mild, progression to generalised tetanus can occur. Cephalic tetanus is the rarest form of tetanus. It is associated with lesions of the head or face, and also has been described in association with ear infections (i.e., otitis media). The incubation period is short, usually 1-2 days. Unlike generalised and localized tetanus, cephalic tetanus results in flaccid cranial nerve palsies rather than spasm. Trismus may also be present. Like localized tetanus, cephalic tetanus can progress to the generalised form.

Pertussis

In classic disease, mild upper respiratory tract symptoms begin 7-10 days (range 6-21 days) after exposure, followed by development of a cough that becomes paroxysmal. Coughing paroxysms can be frequent or relatively infrequent and are often followed by vomiting. Fever is absent or minimal. Young infants may present with apnoea before significant cough develops. In older infants and young children, an inspiratory whoop may be generated at the end of a coughing spell. Recently immunised children may have mild cough illness; older children and adults may have prolonged cough with or without paroxysms. The cough gradually wanes over several weeks to months. Serious complications are most common in young, unvaccinated infants and include apnoea, seizures, pneumonia, weight loss, and rarely, death.

Prevention

Vaccine

Immunisations for Infants and Children <7 Years of Age

Simultaneous immunisation against diphtheria, tetanus, and pertussis during infancy (see Tables 8-2 and 8-3) is recommended. Combination vaccines contain diphtheria and tetanus toxoids and either whole-cell pertussis antigens (DTwP) or acellular pertussis antigens (DTaP). Neither DTwP nor DTaP pertussis vaccine is licensed for persons 7 or more years of age. DTwP vaccine is no longer available in the United States.

Three brands of DTaP currently are approved for use and are available in the United States. Whenever possible, the same brand of DTaP vaccine should be used for all doses of the vaccination series; however, any licensed DTaP vaccine may be used to continue or complete the vaccination series if the type of vaccine previously administered is not known or the type of vaccine used for earlier doses is not available.

Immunisation for infants and children up to the seventh birthday consists of five doses of DTaP vaccine. The first three doses are usually given at ages 2, 4 and 6 months, the fourth dose at age 15-18 months, and the fifth dose at age 4-6 years. The fifth dose is not necessary if the fourth dose was given after the child's fourth birthday.

Three—and preferably four—doses of DTaP are necessary for protection against diphtheria, tetanus and pertussis. Travellers should be advised to complete as many doses as possible of the primary series before travelling. If an accelerated schedule is required to complete the series of DTaP vaccine, the schedule may be started as soon as the infant is 6 weeks of age, with the second and third doses given 4 weeks after each preceding dose (Table 8-3). The fourth dose should not be given before the child is age 12 months and should be separated from the third dose by at least 6 months. The fifth dose should not be given before the child is age 4 years. Interruption of the recommended schedule or delay in doses does not lead to a reduction in the level of immunity reached on completion of the primary series. There is no need to restart a series regardless of the time that has elapsed between doses. For infants and children age <7 years with a contraindication to the pertussis component of DTaP, diphtheria-tetanus (DT) should be used (Table 8-2).

Immunisations for Children 7 or More Years of Age, Adolescents, and Adults

Children greater than or equal to7 years of age, adolescents, and adults should receive the adult formulation of tetanus and diphtheria toxoids (Td) whenever either tetanus or diphtheria toxoid is indicated (Tables 8-2 and 8-3; no pertussis vaccine is licensed for use in adults). Anyone greater than or equal to7 years of age who has not received a primary series against tetanus and diphtheria should receive three doses of Td; the first two doses should be given 4-8 weeks apart and the third dose 6-12 months after the second. Two doses of Td received at intervals of at least 4 weeks can provide some protection, but a single dose is of little benefit. In the rare instance when administration of the third dose following a 6- to 12-month interval cannot be ensured, the third Td dose can be given 4-8 weeks after the second dose to complete the primary series. Anyone whose history of primary tetanus and diphtheria vaccination is uncertain should be considered unvaccinated and should receive the three-dose series. Anyone who has received only one or two prior doses of tetanus and diphtheria toxoids should receive additional doses to complete the three-dose series. The first booster dose of Td should be given when the child is 11 or 12 years of age if at least 5 years has elapsed since the last dose of DTaP or paediatric DT. Thereafter, routine booster doses of Td should be given every 10 years.

Adverse Reactions

Local reactions (erythema and induration with or without tenderness) are common after the administration of vaccines containing diphtheria, tetanus, and pertussis antigens. Mild systemic reactions such as fever, drowsiness, fretfulness, and low-grade fever can occur after vaccination with DTaP. These reactions are self-limited and can be managed with symptomatic treatment of Paracetamol (acetaminophen in USA) (paracetamol) or ibuprofen. Reports of moderate to severe systemic events (e.g., fever 40.5°C or higher [105°F or higher], febrile seizures, persistent crying lasting 3 hours or more, and hypotonic-hyporesponsive episodes) have been uncommon after administration of DTaP and they have occurred less frequently among children administered DTaP than those administered DTwP. Swelling involving the entire thigh or upper arm has occurred after the fourth and fifth doses of DTaP. These reactions are also self limited.

Anaphylactic and other serious adverse reactions are rare after receipt of preparations containing diphtheria, tetanus or pertussis components, or a combination of these. Arthus-type hypersensitivity reactions, characterised by severe local reactions, have been reported in adults who received frequent boosters of tetanus or diphtheria toxoids.

Precautions and Contraindications

An immediate anaphylactic reaction to a prior dose of vaccine or vaccine component is a contraindication to further vaccination with DTaP, DT, or adult Td. Encephalopathy not due to another identifiable cause within 7 days of vaccination is a contraindication to further vaccination with a pertussis-containing vaccine.

Moderate or severe acute illness is a precaution to vaccination. Anyone with mild illnesses, such as otitis media or upper respiratory infection, should be vaccinated. Anyone for whom vaccination is deferred because of moderate or severe acute illness should be vaccinated when the condition improves.

Certain infrequent adverse events following pertussis vaccination are considered precautions (not contraindications) to additional doses of pertussis vaccine: a seizure, with or without fever, occurring within 3 days of immunisation; temperature >40.5° C (>105° F) not resulting from another identifiable cause within 48 hours of immunisation; collapse or a shock-like state (hypotonic-hyporesponsive episode) within 48 hours of immunisation, or persistent, inconsolable crying lasting >3 hours and occurring within 48 hours of immunisation. These events have not been proven to cause permanent sequelae. In certain circumstances (e.g., during a communitywide outbreak of pertussis), the benefit of additional vaccination with DTaP may outweigh the risk of another reaction.

Progressive neurologic conditions characterised by changing developmental findings are considered contraindications to receipt of pertussis vaccine. Such disorders include infantile spasms and other epilepsies beginning in infancy. Refer to the American Academy of Paediatrics Red Book for additional information. Infants and children with stable neurologic conditions such as cerebral palsy or controlled seizures should be vaccinated.

Treatment

Patients with respiratory diphtheria require hospitalization, immediate treatment with diphtheria antitoxin, appropriate antibiotics, and supportive care. Such patients should also receive a dose of a diphtheria toxoid-containing vaccine during the convalescent period.

Close contacts of diphtheria cases should be tested for C. diphtheriae infection, may require antibiotic prophylaxis, and may need vaccination with a diphtheria toxoid-containing vaccine if immunisation status is not up to date.

Tetanus is a medical emergency requiring hospitalization, immediate treatment with tetanus immune globulin (human TIG, or equine antitoxin if human immune globulin is not available) a tetanus toxoid booster, agents to control muscle spasm, and, if indicated, aggressive wound care and antibiotics. Depending on the severity of disease, mechanical ventilation and agents to control autonomic nervous system instability may be required.

Young infants with pertussis often require hospitalization to manage apnoea, hypoxia and feeding difficulties. Antibiotic therapy with a macrolide antibiotic (or trimethoprim/sulfamethoxazole if macrolide is contraindicated) may ameliorate the cough illness if given during the catarrhal stage; once paroxysmal cough has developed, however, antibiotics usually have no effect on the course of illness but are recommended to limit transmission to others. Antibiotic treatment is therefore recommended for persons with pertussis who have cough duration of less than or equal to3 weeks. Prophylaxis (with antibiotics listed above) for close contacts and high-risk contacts of such cases is generally recommended within 3 weeks of exposure, regardless of the age and vaccination status of the contacts. Initiating prophylaxis 3 weeks or more after exposure is usually not of benefit, but can be considered for high-risk contacts (e.g., newborn infants) up to 6 weeks after exposure.

Bibliography
  • CDC. Diphtheria acquired by U.S. citizens in the Russian Federation and Ukraine —1994. MMWR Morb Mortal Wkly Rep 1995; 44:243-44.
  • CDC. Fatal respiratory diphtheria in a U.S. traveller to Haiti —2003. MMWR Morb Mortal Wkly Rep 2003;52:1285-86.
  • Farizo KM, Strebel PM, Chen RT, et al. Fatal respiratory disease due to Corynebacterium diphtheriae: case report and review of guidelines for management, investigation, and control. Clin Infect Dis 1993;16:59-68.
  • Galazka AM. The immunologic basis for immunisation: Tetanus (WHO/EPI/GEN/13.13). Geneva, World Health Organization, 1993. Available at: http://whqlibdoc.who.int/hq/1993/WHO_EPI_GEN_93.13_mod3.pdf
  • Long SS, Pertussis. In: Behrman RE, Kliegman R, Jenson HB, editors. Nelson Textbook of Paediatrics: 16th ed. Philadelphia: W.B. Saunders; 2000. p. 779-84.
  • Lumio J, Olander RM, Grounstorem K, et al. Epidemiology of three cases of severe diphtheria in Finnish patients with low antitoxin antibody levels. Eur J Clin Microbiol Infect Dis 2001; 20:705-10.

- Margaret Cortese, Martha H. Roper, and Tejpratap Tiwari

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